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Biomedical subjects

S Paul

Publications and source records attributed to S Paul.

At least 19 recordsLinked to original sources

Axillary and tympanic membrane temperature measurements are unreliable early after cardiopulmonary bypass.

BACKGROUND AND OBJECTIVE: Inaccurate measurements of body temperature following cardiopulmonary bypass may be associated with serious complications. The purpose of this study was to determine whether axillary and tympanic temperature measurements correlate with the urinary bladder temperature in the early postcardiac surgery period. METHODS: Forty-nine adult patients who underwent cardiac surgery under cardiopulmonary bypass at our institution were prospectively studied. Urinary bladder, right axillary, right tympanic and left tympanic temperature measurements were simultaneously recorded at 0, 6, 12 and 18 h following cardiopulmonary bypass. Patients had one to four sets of recordings and a total of 629 temperature measurements were recorded. The mean difference (bias) between the bladder and each of the other methods and limits of agreement were calculated using Bland and Altman method. RESULTS: The mean core body temperature recorded from the bladder on admission to the intensive care unit was 36.4 degrees C. After 6, 12 and 18 h the mean core body temperature was 37.4 degrees C (range: 35.2-39.0), 37.5 degrees C and 37.45 degrees C, respectively. The mean differences (bias) between the bladder temperature and the other three methods were: left tympanic, 0.65 degrees C (95% CI: -0.24 to 1.58); right tympanic, 0.57 degrees C (95% CI: -0.48 to 1.63) and right axillary, 0.55 degrees C (95% CI: -0.27 to 1.36). CONCLUSIONS: The axilla and tympanic membrane are unreliable sites for core body temperature measurement early after cardiopulmonary bypass in adult patients and clinical decisions should be based on more reliable methods.

Adult↗

A semantically enabled formalism for the knowledge management of Parkinson's disease.

Bio-ontology is a formal representation of biological concepts that is used in the interchange of communication between computers and humans alike. They can then be used in the formulation and retrieval of knowledge. In developing a knowledge-based system for Parkinson's Disease, a procedure of knowledge map was used to capture and harness the intellectual resources of an organization, and new paradigms for knowledge mapping were also formulated. Knowledge bases for symptoms and drugs, physiotherapy, speech and language therapy, and dieting that affect patient care were developed. Finally, the knowledge bases were merged to form a single central repository of knowledge base.

Diet↗

Efficiency of specialist rehabilitation in reducing dependency and costs of continuing care for adults with complex acquired brain injuries.

OBJECTIVES: To examine functional outcomes from a rehabilitation programme and to compare two methods for evaluating cost efficiency of rehabilitation in patients with severe complex disability. SUBJECTS AND SETTING: Two hundred and ninety seven consecutive admissions to a specialist inpatient rehabilitation unit following severe acquired brain injury. METHODS: Retrospective analysis of routinely collected data, including the Functional Independence Measure (FIM), Barthel Index, and Northwick Park Dependency Score and Care Needs Assessment (NPDS/NPCNA), which provides a generic estimation of dependency, care hours. and weekly cost of continuing care in the community. Patients were analysed in three groups according to dependency on admission: "low" (NPDS<10 (n=83)); "medium" (NPDS10-24 (n=112)); "high" (NPDS>24 (n=102)). RESULTS: Mean length of stay (LOS) 112 (SD 66) days. All groups showed significant reduction in dependency between admission and discharge on all measures (paired t tests: p<0.001). Mean reduction in "weekly cost of care" was greatest in the high dependency group at pound639 per week (95% CI 488 to 789)), as compared with the medium (pound323/week (95% CI 217 to 428)), and low (pound111/week (95% CI 42 to 179)) dependency groups. Despite their longer LOS, time taken to offset the initial cost of rehabilitation was only 16.3 months in the high dependency group, compared with 21.5 months (medium dependency) and 38.8 months (low dependency). FIM efficiency (FIM gain/LOS) appeared greatest in the medium dependency group (0.25), compared with the low (0.17) and high (0.16) dependency groups. CONCLUSIONS: The NPDS/NPCNA detected changes in dependency potentially associated with substantial savings in the cost of ongoing care, especially in high dependency patients. Floor effects in responsiveness of the FIM may lead to underestimation of efficiency of rehabilitation in higher dependency patients.

Activities of Daily Living↗

T-cell sensitisation to hepatitis B virus surface antigens.

The present study was conducted to explore the immunity to hepatitis B surface antigens (HBsAg) of ad and ay subtypes at the cellular level among adult individuals. Peripheral blood mononuclear cells (PBMCs) obtained from acute hepatitis B virus (HBV) infected patients, chronic HBV infected patients, recovered subjects from HBV infection and uninfected vaccinated controls were stimulated with HBsAg ad and HBsAg ay subtypes in vitro. Stimulated PBMCs were incubated in CO(2) for production of interferon-gamma (IFN-gamma), which was measured from the supernatant of cultured PBMCs by an in-house ELISA technique. The mean +/- SE of IFN-gamma levels produced by PBMCs in response to HBsAg ad among the acute, chronic, recovered and control groups were 282.5+/-134.51 pg/ml, 307.45+/-94.84 pg/ml, 915.62+/-170.80 pg/ml and 511.67+/-161.22 pg/ml respectively, while on stimulation by HBsAg ay, the levels were 246.25+/-103.50 pg/ml, 374.70+/-104.02 pg/ml, 1040 +/-140.76 pg/ml and 465.83+/-166.26 pg/ml respectively among the above mentioned groups. The results of this study showed that PBMCs were non-responsive to stimulation by both HBsAg ad and HBsAg ay subtypes in acute and chronic patients with HBV infection. The recovered group responded significantly to both subtypes of HBsAg and the control group did not. The study indicates that although the patients with acute and chronic HBV infection showed weak or no IFN-gamma response to the HBsAg, subjects showed strong IFN-gamma response to the surface antigens on recovery from HBV infection.

Acute Disease↗

Recruitment of sperm donors: the Newcastle-upon-Tyne experience 1994-2003.

BACKGROUND: The demand for sperm donors has continued despite the introduction of ICSI. This study was undertaken in the light of impending changes in donor anonymity laws to evaluate the recruitment process of sperm donors. METHODS: Retrospective analysis of 1101 potential sperm donors in a tertiary referral centre between January 1994 and August 2003. The main outcome measures were to determine the demographic details, recruitment rate and reasons for rejection of donors. RESULTS: The majority of the applicants were aged <36 years (88.07%), students (54.88%), without a partner (53.47%), unmarried (85.38%) and without proven fecundity (78.67%). Only 3.63% of the applicants were released as donors, 30.79% defaulted, whilst 64.48% were rejected. The most common reason for rejection was suboptimal semen quality (85.07%). Over the years, the numbers of the applicants and released donors have declined significantly. The overall clinical pregnancy rate from donor sperm during this period was 23.52%. CONCLUSIONS: In this successful anonymous sperm donor programme only a small proportion of the applicants are released as donors. The significant decline in released sperm donors coupled with the potential effects of loss of donor anonymity means that new strategies for sperm donor recruitment are urgently required.

Adult↗

Antimicrobial activity of chitosan against vibrios from freshwater prawn Macrobrachium rosenbergii larval rearing systems.

Chitosan is a biocompatible and biodegradable natural polymer with established antimicrobial properties against specific microorganisms. The present study demonstrates its antibacterial activity against 48 isolates of Vibrio species from prawn larval rearing systems. The antibacterial activity had a positive correlation with the concentration of chitosan. This work opens up avenues for using chitosan as a prophylactic biopolymer for protecting prawn larvae from vibriosis.

Animals↗

A comparison of immunohistochemical and silver staining methods for the detection of diffuse plaques in the aged canine brain.

Plaques and amyloid angiopathy represent frequent findings in the aging canine brain, whereas neuritic (senile) plaques and neurofibrillary tangles, the hallmark of Alzheimer's disease in humans, have only rarely been described in this species. Most studies on canine age-related CNS changes have used the modified (mod.) Bielschowsky method. Therefore, it remains to be determined, whether results obtained represent species-specific age-related changes or are due to the use of inappropriate methods. Consequently, the aim of this study was to compare the usefulness of various methods for the detection of age-related changes in the canine CNS. In a preliminary study, 130 brains from dogs between 1 month and 18 years of age were screened for the presence of A-beta protein using a monoclonal antibody against the beta-amyloid peptide. Thereafter, 30 brains of aged dogs, 10-18 years of age, out of the 130, were comparatively investigated by immunohistochemistry and silver stains such as the method of Campbell-Switzer, Reusche, Gallyas, modified (mod.) Bielschowsky and mod. Bodian as well as the Congo red-stain. Vascular amyloid angiopathy, plaques and A-beta protein deposits in the hippocampus/dentate gyrus were an age-dependent process starting at the age of 8 years and increased in a linear fashion with age. In contrast, plaque density did not rise in a similar age-related fashion in aged dogs. Moreover, great individual variations were observed in aged animals. Immunohistology was by far the most sensitive method for detection of diffuse plaques and amyloid angiopathy, followed by the Campbell-Switzer, Reusche, mod. Bielschowsky, and mod. Bodian technique. Neurofibrillary tangles and Congo red positive neuritic plaques were not found with any method. Immunohistochemically, two plaque types, both resembling diffuse human plaques, occurring in the superficial or deep cortical layers, were detected. Cluster analysis suggested the presence of three subgroups such as aged dogs with a low, medium and high number of plaques. Summarized, detection of plaques depends strongly upon the method used and the aging canine brain displays diffuse plaques and amyloid angiopathy but lacks neurofibrillary tangles and classic/neuritic and Congo red positive plaques. Cluster analysis indicated, that genetic factors might be important as predisposition for the development of diffuse plaques in dogs. The observed findings substantiate previous observations, that the canine brain represents an important model to study the pathogenesis of diffuse plaques and amyloid angiopathy in the absence of other Alzheimer disease characteristic lesions.

Age Factors↗

Human subtelomere structure and variation.

Work towards completion of the human reference genome sequence has revealed a great deal of complexity and plasticity in human subtelomeric regions. The highly variable subtelomeric repeat regions are filled with recently shuffled genomic segments, many of which contain sequences matching transcripts and transcript fragments; the rapid duplication and combinatorial evolution of these regions has generated an extremely diverse set of subtelomeric alleles in the human species, the complexity and potential significance of which is only beginning to be understood. This review summarizes recent progress in analyzing human subtelomeric sequence assemblies and large-scale variation in human subtelomere regions.

Genetic Variation↗

CHHIPS (Controlling Hypertension and Hypotension Immediately Post-Stroke) Pilot Trial: rationale and design.

RATIONALE: High and low blood pressure (BP) levels are common following acute stroke, with up to 60% of patients being hypertensive (SBP > 160 mmHg) and nearly 20% having relative hypotension (SBP < or = 140 mmHg), within the first few hours of ictus, both conditions being associated with an adverse prognosis. At present, the optimum management of blood pressure in the immediate post-stroke period is unclear. OBJECTIVE: The primary aim of the Controlling Hypertension and Hypotension Immediately Post-Stroke (CHHIPS) Pilot Trial is to assess whether hypertension and relative hypotension, manipulated therapeutically in the first 24 h following acute stroke, affects short-term outcome measures. DESIGN: The CHHIPS Pilot Trial is a UK based multi-centre, randomized, double-blind, placebo-controlled, titrated dose trial. SETTING: Acute stroke and medical units in teaching and district general hospitals, in the UK. PATIENTS: The CHHIPS Pilot Study aims to recruit 2050 patients, with clinically suspected stroke, confirmed by brain imaging, who have no compelling indication or contraindication for BP manipulation. STUDY OUTCOMES: The primary outcome measure will be the effects of acute pressor therapy (initiated < or = 12 h from stroke onset) or depressor therapy (started < or = 24 h post-ictus) on death and dependency at 14 days post-stroke. Secondary outcome measures will include the influence of therapy on early neurological deterioration, the effectiveness of treatment in manipulating BP levels, the influence of time to treatment and stroke type on response and a cost-effectiveness analysis.

Acute Disease↗

Amnesic shellfish poison.

Amnesic shellfish poisoning (ASP) is caused by consumption of shellfish that have accumulated domoic acid, a neurotoxin produced by some strains of phytoplankton. The neurotoxic properties of domoic acid result in neuronal degeneration and necrosis in specific regions of the hippocampus. A serious outbreak of ASP occurred in Canada in 1987 and involved 150 reported cases, 19 hospitalisations and 4 deaths after consumption of contaminated mussels. Symptoms ranged from gastrointestinal disturbances, to neurotoxic effects such as hallucinations, memory loss and coma. Monitoring programmes are in place in numerous countries worldwide and closures of shellfish harvesting areas occur when domoic acid concentrations exceed regulatory limits. This paper reviews the chemistry, sources, metabolism and toxicology of domoic acid as well as human case reports of ASP and discusses a possible mechanism of toxicity.

Amnesia↗

Lithium decreases secretion of Abeta1-42 and C-truncated species Abeta1-37/38/39/40 in chicken telencephalic cultures but specifically increases intracellular Abeta1-38.

We studied endogenous amyloid precursor protein (APP) processing and amyloid beta (Abeta) peptide formation in primary chicken telencephalic neurons, because their Abeta peptide sequence is identical to humans. As detected by quantitative Abeta-SDS-PAGE/immunoblot, Abeta peptides 1-40/42 and three additional C-truncated species, namely Abeta1-37/38/39 were regularly released into the supernatant. The highly conserved Abeta quintet strongly resembles the pattern of Abeta peptides found in human cerebrospinal fluid. Furthermore, the C-terminally shorter Abeta peptides 1-33/34 could be readily detected. Recent evidence indicates that lithium specifically inhibits secretion of the amyloidogenic Abeta1-42 peptide in cultured permanent cells transfected with human APP. We therefore investigated the effect of lithium on Abeta peptide secretion as well as intracellular Abeta peptides in our untransfected primary cell culture system. Our data shows that lithium leads to a dose-dependent reduction of Abeta1-37/38/39/40/42 secretion. Surprisingly, intracellular analysis revealed that lithium specifically increases a band comigrating with synthetic Abeta1-38 while Abeta1-40 and Abeta1-42 remained almost unaffected. These results demonstrate for the first time that lithium treatment decreases Abeta peptide secretion in primary chicken neuronal cells but specifically elevates intracellular Abeta1-38. Therefore, we conclude that there are two independent mechanisms of lithium in intra- and extracellular Abeta peptide production.

Amyloid beta-Peptides↗

The DGAT1 K232A mutation is not solely responsible for the milk production quantitative trait locus on the bovine chromosome 14.

The gene, acyl-CoA:diacylglycerol acyltransferase1 (DGAT1), was recently identified as the one underlying the quantitative trait locus (QTL) for milk production traits in the centromeric region of the bovine chromosome 14. Until now, 2 alleles, the lysine variant (increasing fat yield, fat and protein percentage) and the alanine variant (increasing protein and milk yield), were postulated at DGAT1. This study investigated whether the diallelic DGAT1 polymorphism is responsible for all the genetic variation at the centromeric region of this chromosome for milk, fat, and protein yield and fat and protein percentage. A statistical model was applied to a granddaughter design to analyze 16 German Holstein families. The model included the diallelic DGAT1 effect and the QTL transition probability estimated for each chromosomal position by a multiple marker approach. Because the regression coefficient of this probability was corrected for the diallelic DGAT1 polymorphism, it represented a putative conditional QTL effect. The effect of the DGAT1 gene was always highly significant. The conditional QTL effect was significant genomewise for fat percentage at the proximal end of the chromosome and for protein percentage at a more distal chromosomal region. Additional chromosomewise significance was found for fat and protein yield. Our results suggest an additional source of genetic variance on this chromosome for these traits; either one or more additional alleles segregating at DGAT1 that were not previously detected, a second quantitative trait locus affecting these traits, or both.

Acyltransferases↗

Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

OBJECTIVE: The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated. METHODS: In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography. RESULTS: FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet. CONCLUSION: This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.

Adolescent↗

A study on interferon-gamma (IFN-gamma) response by T cells stimulated by hepatitis B virus core antigen.

Cell-mediated immune response by lymphocyte induced through recognition of HBV core antigen during acute HBV infection, chronic HBV infection and in subjects recovered from HBV infection was investigated in the present study by assessing the competence of IFN-gamma secretion by cultured PBMCs on stimulation by HBV nucleocapsid antigen (HBcAg). Fresh blood was collected in heparin from acute, chronic and recovered groups of HBV infected patients and uninfected vaccinated healthy controls aged between 18-50 years. PBMCs were separated by Ficoll-Hypaque density gradient centrifugation technique and were stimulated with hepatitis B virus core antigen (HBcAg) and mitogen (lectin). Stimulated PBMCs were cultured in CO2 and IFN-gamma levels were measured from the culture supernatant by an in-house ELISA technique. The mean+/-SE levels of IFN-gamma in HBcAg stimulated PBMCs in acute, chronic, recovered and controls groups were 875 pg/ml+/-297.56, 128.50 pg/ml+/-33.66, 905 pg/ml+/-172.51 and 235.33 pg/ml+/-111.28 respectively. IFN-gamma levels produced by HBcAg stimulated PBMCs of acute and recovered groups were significantly higher than that of chronic and control group (p<0.001). All groups responded strongly to lectin stimulation. Thus, it may be concluded that patients with acute HBV infection and those who had recovered from HBV infection show vigorous response to HBcAg stimulation in contrast to patients with chronic HBV infection.

Acute Disease↗